L-165,041, troglitazone and their combination treatment to attenuate high glucose-induced receptor for advanced glycation end products (RAGE) expression

Liang, Yao-Jen; Jian, Jhin-Hao; Chen, Chao-Yi; Hsu, Chia‐Yu; Shih, Chin-Yu; Leu, Jyh-Gang

doi:10.1016/j.ejphar.2013.06.026

Cited by 10 publications

(8 citation statements)

References 24 publications

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“…The current findings uncover important roles for PPARG in the mechanisms of CML-AGE/RAGE–dependent reduction in expression of ABCA1 and ABCG1 . Although PPARG agonists may exert their effects at least partly through downregulation of Ager ( 44 , 45 ), the present findings suggest that the converse is also true; that is, RAGE ligands directly suppress PPARG through ERK signal transduction. Previous work has suggested that CML-AGE reduces PPARG expression in chondrocytes ( 40 ); the current study illustrates new roles for AGE/RAGE in the suppression of PPARG in macrophages and suggests a potential novel role for the AGE/RAGE pathway in distinct effects of PPARG, such as macrophage polarization ( 37 – 39 ).…”

Section: Discussionmentioning

confidence: 56%

RAGE Suppresses ABCG1-Mediated Macrophage Cholesterol Efflux in Diabetes

et al. 2015

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Diabetes exacerbates cardiovascular disease, at least in part through suppression of macrophage cholesterol efflux and levels of the cholesterol transporters ATP binding cassette transporter A1 (ABCA1) and ABCG1. The receptor for advanced glycation end products (RAGE) is highly expressed in human and murine diabetic atherosclerotic plaques, particularly in macrophages. We tested the hypothesis that RAGE suppresses macrophage cholesterol efflux and probed the mechanisms by which RAGE downregulates ABCA1 and ABCG1. Macrophage cholesterol efflux to apolipoprotein A1 and HDL and reverse cholesterol transport to plasma, liver, and feces were reduced in diabetic macrophages through RAGE. In vitro, RAGE ligands suppressed ABCG1 and ABCA1 promoter luciferase activity and transcription of ABCG1 and ABCA1 through peroxisome proliferator–activated receptor-γ (PPARG)–responsive promoter elements but not through liver X receptor elements. Plasma levels of HDL were reduced in diabetic mice in a RAGE-dependent manner. Laser capture microdissected CD68+ macrophages from atherosclerotic plaques of Ldlr−/− mice devoid of Ager (RAGE) displayed higher levels of Abca1, Abcg1, and Pparg mRNA transcripts versus Ager-expressing Ldlr−/− mice independently of glycemia or plasma levels of total cholesterol and triglycerides. Antagonism of RAGE may fill an important therapeutic gap in the treatment of diabetic macrovascular complications.

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Section: Discussionmentioning

confidence: 56%

RAGE Suppresses ABCG1-Mediated Macrophage Cholesterol Efflux in Diabetes

et al. 2015

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“…In vitro and diabetic animal model studies have confirmed the beneficial role of PPARγ in diabetic kidney disease 27 28 . To examine potential miRNAs that regulate PPARγ expression, we utilized computational prediction programs (TargetScan, PicTar, miRanda, and miRGen) to identify potential binding sites for miRNAs in the PPARγ-3′-UTR.…”

Section: Resultsmentioning

confidence: 88%

MicroRNA-27a Induces Mesangial Cell Injury by Targeting of PPARγ and its In Vivo Knockdown Prevents Progression of Diabetic Nephropathy

Wang

Guo

et al. 2016

Sci Rep

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MicroRNAs play important roles in the pathogenesis of diabetic nephropathy (DN). In this study, we found that high glucose upregulated miR-27a expression in cultured glomerular mesangial cells and in the kidney glomeruli of streptozotocin (STZ)-induced diabetic rats. miR-27a knockdown prevented high glucose-induced mesangial cell proliferation and also blocked the upregulation of extracellular matrix (ECM)-associated profibrotic genes. Reduction of cell proliferation and profibrotic gene expression by a miR-27a inhibitor depended upon the expression of peroxisome proliferator-activated receptor γ (PPARγ). Further studies showed that miR-27a negatively regulated PPARγ expression by binding to the 3′-untranslated region of rat PPARγ. An antisense oligonucleotide specific to miR-27a (antagomir-27a) significantly reduced renal miR-27a expression in STZ-induced diabetic rats and significantly increased PPARγ levels. Antagomir-27a also reduced kidney ECM accumulation and proteinuria in STZ-induced diabetic rats. These findings suggest that specific reduction of renal miR-27a decreases renal fibrosis, which may be explained in part by its regulation of PPARγ, and that targeting miR-27a may represent a novel therapeutic approach for DN.

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“…In this study, 0.3 nM exendin-4 showed similar anti-inflammatory potency on RMC to 1 μM L-165,041. In previous studies, 1 μM L-165,041 was able to decrease CRP-induced IL-6 expression in rat cardiomyocytes [ 16 ] and human umbilical vein endothelial cells [ 17 ], and shared similar potency to another PPARδ agonist, troglitazone (10 μM), in inhibiting high glucose (25 mM)-induced inflammation and apoptosis in mesangial cells [ 18 ]. GLP-1 receptor agonists and dipeptidyl peptidase IV (DPP-4) inhibitors are being widely used in clinical treatment.…”

Section: Discussionmentioning

confidence: 99%

Glucagon-like peptide receptor agonists attenuate advanced glycation end products-induced inflammation in rat mesangial cells

Chang¹,

Liang

Hsu

et al. 2017

BMC Pharmacol Toxicol

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BackgroundHyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production play major roles in progression of diabetic nephropathy. Anti-RAGE effect of peroxisome proliferator-activated receptor-delta (PPARδ) agonists was shown in previous studies. PPARδ agonists also stimulate glucagon-like peptide-1 (GLP-1) secretion from human intestinal cells.MethodsIn this study, the individual and synergic anti-inflammatory effects of GLP-1 receptor (exendin-4) and PPARδ (L-165,041) agonists in AGE-treated rat mesangial cells (RMC) were investigated.ResultsThe results showed both exendin-4 and L-165,041 significantly attenuated AGE-induced IL-6 and TNF-α production, RAGE expression, and cell death in RMC. Similar anti-inflammatory potency was seen between 0.3 nM exendin-4 and 1 μM L-165,041. Synergic effect of exendin-4 and L-165,041 was shown in inhibiting cytokines production, but not in inhibiting RAGE expression or cell death.ConclusionsThese results suggest that both GLP-1 receptor and PPARδ agonists have anti-inflammatory effect on AGE-treated rat mesangial cells.

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L-165,041, troglitazone and their combination treatment to attenuate high glucose-induced receptor for advanced glycation end products (RAGE) expression

Cited by 10 publications

References 24 publications

RAGE Suppresses ABCG1-Mediated Macrophage Cholesterol Efflux in Diabetes

RAGE Suppresses ABCG1-Mediated Macrophage Cholesterol Efflux in Diabetes

MicroRNA-27a Induces Mesangial Cell Injury by Targeting of PPARγ and its In Vivo Knockdown Prevents Progression of Diabetic Nephropathy

Glucagon-like peptide receptor agonists attenuate advanced glycation end products-induced inflammation in rat mesangial cells

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